Apparatus for detecting vasospasm



April 27, 1954 L.. R. KRAsNo APPARATUS FOR DETECTING vAsosPAsM Filed Oct. 18, 1949 Patented Apr. 27, 1954 ,APPARATUS FOR DETECTINQ YeSQsPASM Louis R. Krasno, Evanston, Ill., assigner to `Clini- .cal Instruments Company, Chicago, vIl l., a cor.-

ncration pf Illinois applicati@ @sicher .18, 1949, Serial .Ne .1.212.970

(o1. ssa-20 This invention is directed to a new, improved, and useful method or detecting vasospasm in the human body whereby the presence of subclinical and potential heart disease may be determined.

This invention is alse concerned Iwith a new `and improved apparatus for the physiological measurement of't-he flicker fusion threshold of a patient whereby vasospasm may be detected.

In recent years the importance of diseases ol the human heart as a threat to `a healthy civilization has been real-izedby more and more members of the medical profession 4throughout the World. important discoveries and contributions in the field of cardiovascular `medicine have :been made in the effort to combat this dreaded enemy of the public. Nevertheless, the 'maiority of these efforts have been l,directed toward the therapeutic rather than the prophylactic approach. The need for a successful method of `detecting the presence of incipient heart disease `has been felt all who have attacked the problem.

The use of the electrocardiograph has admittedly done much to aid the treatment of heart disease. However, this method is of clinical value primarily only Iafter the disease has made its appearance Lin the -form of `fully .developed damage to the heart. It is imperative, therefore, that lthe medical World have vsome reliable means whereby the abnormal processes leading to a myocardial infarction, hypertension, coronary insufiiciency and angina pectoris may be -detected before such serious rdamage to the heart occurs.

I propose to malge snch an early detection of heart disease by determiningv lthe presence of vasospasm which is unphysiological and does not normally exist in the human body, the presence of which is consistently found to-be associated with the aforementioned established abnormal cardiovascular conditions.

Other methods of Adi,s'coverinug yasospasrn lhave not been Very successful due to theirdependence on physiological .indicia which .represent abnormal anatomical changes. One `s uch method is that of taking the skintemperatures of a patient, which method depends on absolute readings of the recording 4instrument and variations of the skin temperature. All of these methods depend largely on the blood vessels :of the extremities which, because Aof their anatomic structure, are by no means vas sensitive .and as indicative `of what is taking'pl'ace withinthecardiovascular sys.. tem as are the `bloodvessels of the lbrain and .retina, which-vessels mym-ethod employslbyuseof the flickeriusion-test. #These-methods require equipmen-t and procedures too complicated to make ita practical oice procedure. Some methods re.- quife attachments of instruments to the skin of the extremities While other procedures involve the injection of radioactive materials into the circulation of the patient. This makes for additional inconvenience `to the doctor and the patient and still involves blood vessels of the extremities which are structurally different from those ci the retina. These disadvantages are obviated with the present method.

During World War AII extensive experiments were conducted with reerenceto .anoxia and fatigue cf Athe central nervous system. These wereconce'rned with `anoxia occurring vduring high altitude flying .by airplane pilots. Such anoxia, or lack or oxygen vsupply to the tissues o the body, Was most .successfully detected by the flicker :fusion test, which indicated pilot anoxia and fatigue long .before any .other tests or .symptoms made this condition apparent. `Such anoxia was `termed innocuous, that is, non-apparent anoxia. Under normal atmospheric .condif tions with a normal supply vof oxygen present, a normal person should Ynot suffer from anoxia, providing, of coursejthat he has anormal cardiovascular system. Therefore, if a normal person develops .the `findings lof anoxia at .ground level, it would indicate some abnormality in his circulatory system which supplies the body tissue with needed oxygen. YSuch an abnormality of impairment of the circulation, and thus an impairment of the supply of .oxygen to the body tissues, apparentlyis yassociated With vasospasrh at a -very early stage in the development of abnormal cardiovascular conditions.

The hereinafter described method of detecting heart disease adopts the `premise that .since hypertensive and coronary .cardiovascular disease `is ultimately and physiologically expressed by the appearance of tissue anoxia, there existsan finnocuousanoxiain the early cardiac patient .associated with lvasospasm. This innocuous .or non-apparent anoxia may .not be detectable -by any of the vhnoi'vn methods .of examination. Further, it may not `beassociated with any detectable anatomic change of symptoms, and the .patient may be entirely `unaware of :its presence.

`It is .an `object of my 1invention to .describe a method Whereby'theseearly physiologicalchanges `of cardiovascular.diseasefxnaybe easily and ,readily .dctected.

V.l1-,isa -further .obj-ect of .my invention to Ypresent a simple and reliable method which `can .be used in the normal routine of .ollceexarninations to 3 detect an early tendency to hypertensive or coronary heart diseases.

It is a further object of my invention to describe a new and improved method of detecting an early tendency to hypertensive and coronary heart disease by means of a comparison of flicker fusion performance before and after the admini stration of a drug to the patient which indicates the presence of vasospasm.

It is a still further object of my invention to provide a new and improved electronic device for the physiological measurement of a patients flicker fusion threshold. These and further objects will appear in the following description.

In order to acquaint those skilled in the art with the hereinafter described method of detect ing vasospasm, and with the construction and utilization of a device related to this method, a description of a preferred embodiment of the testing device portions of this invention will be made with reference to the accompanying drawings, wherein:

Figure 1 is a schematic diagram of the main elements of a ilicker fusion testing machine made in accordance with this invention;

Figure 2 shows a circuit diagram of the man chine displayed schematically in Figure 1.

The flicker fusion test is made by means of a constant light source which is intermittently cut off from the observer by interposing a shield at varying frequency. As a consequence, the light appears to flicker on an 01T. The frequency rate at which the flickering light flashes appears to the observer as an uninterrupted beam of light is known as the flicker fusion threshold (F. T.) for that individual. If anoxia is present, the F. F. T. lessens-that is, the frequency with which the beam of light is being intermittently shielded must be reduced before the patient can detect a flicker. therapeutic methods, the F. F. T. will and the patient can detect interruptions in the beam of light at greater frequencies. A. probatlve treatise on the fiicker fusion test is to be found in the book entitled Medical Physics by Gtto Glasser, volume II, pages 335 to 339, 1950 edition by The Year Book Publishers, or Chicago, Illinois, wherein the prior developments and uses of flicker fusion phenomena are set forth more fully.

Prior to the invention of the herein disclosed testing device, the fiicker fusion test has generally been conducted by one of two well-known types of testing machines. One type consists of a standard, direct or alternating current-driven motor, which drives a two or four-bladed fan, so that the fan blades intercept the beam of light produced by a tungsten filament light bulb. The motor speed is generally varied by a variable resistance rheostat and the revolutions per minute are read off a moving tachometer pointer. The fact that the pointer is in motion causes some error in the taking of readings with a machine of this general type. The other type which has been used in the past has an electrically produced flickering light based on a frequency oscillator type of arrangement, similar to that used in neon or gas filled bulbs or tubes. A serious difliculty encountered with this latter type of testing device is the lag in the appearance and disappearance of the light. This results in an indenite flicker and thus in erroneous readings.

The device shown schematically in Figure l overcomes the above objections a-nd combines several mechanical and electrical advantages in a single compact machine.

When anoxia is overcome, by various Referring now to Figures 1 and 2 of the drawings, a iiicker fusion testing machine, indicated generally at I0, comprises generally a power supplying transformer Il supplying a low voltage rectifier I2 with alternating current, which it rectiiies to supply a direct current light source i3 interrupted by a cylindrical shutter if! which controls the emission of light through a window iS in an outer casing il surrounding the machine. [i glass window pane I8 may be provided to evenly diffuse the light beams coming through window iii. A synchronous motor I9 is provided to rotate the shutter It and may be controlled, as shown herein by control means of an amplifier 2t fed by a suitable oscillator 2| whose frequency is varied by a suitable tuning condenser 22 controlled by a tuning control knob 23. Means for indicating and recording the frequency of interrupting the light source is shown generally at 2t, and comprises an indicating scale 26 having a movable index pointer 2l controlled and moved by turning a suitable ndex knob 28 and a similar control pointer 29 movable along scale 26 in response to the rotating movement of control knob 23. The control pointer 29 is used for indicating the flicker rate of the light as determined by the patient after the administration of a vasodilating drug, which post drug reading is compared with the initial frequency of the light detectable by the patient before drug administration and recorded on scale 26 by the index pointer 2l'.

Coming now to the details of the several electronic circuits involved in this machine, as set forth in diagrammatic form in Figure 2, it will be noted that the transformer H may have its primary winding 3l fed by an ordinary household alternating current supply 32 of approximately il? volts at 60 cycles. Other values of power supply may be used with equal facility, depending on the particular circuit values required. An off and on switch 33 may be provided and may be conveniently mounted in the outer casing Il of the machine. The transformer has three secondu ary windings 34, 35 and 35; 34 being a high voltage secondary of approximately 60() volts for supplying anode voltages to the various tubes or the machine, as will appear more clearly later herein; 35 being a low voltage winding supplying approximately 5 volts, and 35 another low voltage winding supplying approximately 6 volts.

The low voltage rectifier l2 may be of a common, well known contact type of such materials as copper sulfide, copper oxide or selenium, and is supplied by the transformer winding 36 for rectifying the alternating current supplied thereby into direct current for supplying energy to the light source I3, which may be as herein shown, a direct current bulb, to insure a steady light. A high frequency alternating current bulb would be equally effective if the frequency were sufliciently high to insure imperceptible dicker of the light. A filter condenser 40 may be placed in circuit between the rectifier l2 and the light source I3 to smooth out the rectified current and is herein of a high capacity, 1060 mf., low volttage, l5 v., type.

The low voltage secondary winding 35 of the transformer energizes a filament 4| of a high vacuum, full wave, thermionic rectiiier tube 42 which is shown herein as a conventional 5Y3 tube. The tube 42 supplies pulsating, direct ourrent which is ltered by a pi network comprised herein of a pair of 20-20 mf., 450 v. condensers d3, and a 20 henry choke 44, which network serves to smooth out the high voltage D. C. supplied by the 5Y3 rectifier tube for supplying the anodes of further tubes in the circuit and the field windings of the motor i9, as will appear more clearly hereinafter.

The oscillator 2| may be of a standard R.C. type, as shown herein, having a variable component consisting of a frequency control section composed chiey of a dual section -350 mmf. range control, indicated generally at 4E. Each section it of the range control may have a condenser lil, herein shown as 150 mmf. A resistor d3, herein of 4.4 megohms, which determines the range of frequency control, is grounded to the chassis. A tuning condenser 22 is also employed with the sections 4'6 and may be of the ordinary radio gang plate type, adapted to be tuned by turning the control knob '23 associated with the indicating means 24.

The remaining section of the oscillator circuit contains a twin triode tube 49 connected and used as a resistance coupled amplifier and, as shown herein, may be a standard, commercially available, GSN'T type tube. The two triode members 50 and 5l, enclosed 'in a common tube 9, have a pair of heaters 52 which are connecte-d in parallel interrelation and supplied by the secondary winding 3e of the transformer. The cathode circuit of veach triode member comprises a parallel resistor-capacitor network including a resistor 53, in the order of 10,000 ohms, and a by-pass capacitor, `in the order of mf., whereby a low impedance A.C. path lis provided therefor. A condenser 55, herein a 0.1 mf., 400 v. condenser, couples the plate or "anode o the triode unit Eil to the grid circuit of the triode unit 5l, a grid resistor `5l providing a D.C. return to ground for the grid of trio'de unit 5I. The plates or anodes of the two section oscillator tube 49 are supplied with positive voltage by the 5Y3 rectier unit and the associated filter circuit comprisingl condensers 43 and choke 44; yconnection ci the plates thereto being effected over plate load resistances 58 and 59 respectively. Resistance 58 may be in the order of 47,000 ohms and resistance 59 in the -order lof 680,000 ohms. Of course, it is apparent that vthe 'various values given for the elements connected with Vthe above described oscillator circuit may be changed, as desired, to present a variety of control ranges, and that all of the circuits associated vwith the oscillator SSN? tube vrcontrol the frequency of oscillation to agreater Aor lesser extent.

ri'he output side of oscillator 2l is coupled to a phase inverter tube 53, 'which is :a medium mu triode tube, such as a conventional 6J5 type having a heater et fed by thesecondary winding 36. The capacitor Si is connected between the plate ci the second section `5I of tube 49 and the grid of phase inverter tube 63. The 'cathode circuit of phase inverter tube 53 includes a resistance 64b, in the order of '3900 rohms which connects the cathode to resistor 64,; the Ylatter being conneste to ground. A grid resistor 65, in the order of 2.2 megohms ris connected between the grid 52 and the resistance 54 toprov-ide the normal grid bias for the'grid of the tube. The plate or anode ci the phase inverter tube 63 is supplied with positive voltage-over a plate load resistance 64o. which is connected to the D.C. supply from tube @l2 and the associated ltering pi network oi choke fifi and condenscrs Allt. Resistors 64 and tta are normally selected to comprise in combination the `required plate load value; .resistance 64a being connected rin the plate circuit in a normal manner and resistance'll "being connected in the cathode to ground circuit. The resistances are normally of equal values and in the disclosed embodiment herein may be in the order of 47,000 ohms. The plate and cathode of tube t3 are coupled to the succeeding circuit stage by a pair of capacitors l0, 10.

The phase inverter tube 63 supplies voltages to grids 9E and 91 of a low mu twin triode power tube 68, herein, a 6N7 type tube, used as a class C power amplifier having a common heater 69 fed by the secondary winding 36 of the transformer. Connection with tube 63 is made through a pair of condensers le, 'I3 which may be of 0.1 m1". capacitance. The two grids of the tube 68 are arranged to act out of phase with one another in push-pull relation, thereby using the tube property in which the cathode and plate voltages are 180 out of phase with one another. A pair ci resistors 7i, 1I, herein each having a 47,000 ohm value, are connected between the grids and cathodes of the two sections of the GN? tube BS to furnish the proper operating bias for the tube sections. The output of the rst and second secn tions of tube t8 is supplied to field winding 'i2 of the synchronous motor I9, as each sction is alternatively rendered conductive; the output circuits of these sections being shunted by a 0.5 mf. capacitor lli. A supply conductor 13, extending to the output side of the D.C. voltage supply circuit, is connected to the iield winding 'l2 of the synchronous motor le in center tapped relation whereby the anodes of the two sections of tube 6% are constantly supplied with the necessary B+ voltage.

The motor i9 may be a common, Awell known hysteresis synchronous type havingr an armature of a .suitable magnetic material, with a 220 v. liield coil provided with a .center tap. rIChis type of motor is very similar to that used in present day self-starting electric clocks. As employed h rein, the eld coil has 8100 turns with a center tap therefrom to bring the motor in proper synchronous relation with the driving amplier and other electronic controls of the circuit; -that number of col turns in combination with the 0.5 mi. condenser 14 presenting a proper load value for the GN'T tube. Other turn val-ues may, vof course, be employed, depending on the circuit values required.

The shutter i4 is attached directly to one end of the armature shaft 19a associated with the motor i9 so that the shutter and armature shaft rotate about a common cylindrical axis. The light bulb i3 is adapted to iit within the hollow interior of the shutter built as a cylindrical tube. The shutter is preferably made of a transparent material such as Lucite, glass or like material. A shutter eieot easily is gainedby painting one haii of the transparent shutter, along its cylindrical length, with some opaque material, such as black paint. Since the shutters rotational speed is equal to that of the motor, varying the Arotational speed of the mctor'servesto vary the'speed of the shutter. The aforedescribed electronic system serves to vary the motors speed, the direct control being by manual rotation of the control knob 23 which serves to 'tune the variable condenser 22 for varying the frequency of the oscillator stage 2| and thus'the speed of the shutter rotation is varied as Well. 1t will be noted that shuttering of the light beams prior to .their emission through window le of flashed opal glass or the lilre adjacent the shutter, is accomplished byalternately presenting iirst the transparent and .then the 5 opaque portions of the cylindrical shutter to the window as the shutter rotates with the horizontally disposed armature shaft IBa.

Any suitable metal case l1 may surround the various above described parts to afford a pleasing exterior to the machine and protect the various parts assembled therein.

The indicating scale 2G may be calibrated in rotational cycles per second of the motor or shutter, the frequency of interrupting the light source, or any other suitable units. The index pointer 21 is normally set at the initial average flicker fusion threshold (F. F. T.) of the patient before the administration of nitro glycerin and the control pointer registers the F. F. T. after the nitroglycerin administration, whereby a comparative study between the before and after readings may be made for purposes which will appear more clearly later herein.

The control knob 23 may be connected by a suitable pulley and belt arrangement 25 with the tuning condenser 22 for regulating the frequency of rotation of the shutter. The index control knob 28 may be likewise mounted at the top of the machine case and connected through pulleys and belting to control the movement of the index pointer which acts merely as a recording pointer for a patients normal F. F. T. reading and in no way is connected to the tuning condenser or other electronic units of the machine.

Having thus described a new and improved device for determining the flicker fusion point or threshold of a patient, the purpose and utilization of such a test in determining the presence of vasospasm may appropriately be described.

It is well known in the medical world that vasospasin is an important element in hypertensive and coronary heart disease and that blood circulation is impaired by vasospasm with varying degrees of resultant anoxia. It is an additional fact that nitroglycerin or a like vasodilating drug has a vasodilative eiect on the blood vessels of the body and consequently the vasospastic components of hypertensive and coronary heart disease may be temporarily overcome with the administration of a vasodilator, such as nitroglycerin.

It has also been established that the central nervous system is most sensitive to anoxia. As pointed out above, insensible degrees of anoxia oi the central nervous system as a result of high altitudes have been detected by giving a flicker fusion test to pilots in whom the anoxia was apparently asymptomatic.

Under the influence of a vasodilator, such as nitroglycerin, the flicker fusion threshold of a person with a vasospastic condition will have a characteristic increase due to the improved blood circulation and a temporary decreased anoxia of the central nervous system. A normal individual with no hypertensive or coronary heart disease will have no vasospasm or anoxia. Accordingly, the central nervous system of such a person will not exhibit an increased efliciency after the introduction of nitroglycerin, since the central nervous system is already operating at optimum efficiency as far as the vasospastic component is concerned. In the normal person, the F. F. T. is characteristically decreased because of over dilation by such a vasodilator as nitroglycerin.

The resultant effect of these facts is such as to indicate that the flicker fusion threshold of a patient following the administration of nitroglycerin, will indicate the presence or absence of vasospasm. The presence of vasospasm may be the forerunner of a serious heart disease to appear in the future since it has been found to be associated in over 98% of known cases with hypertensive and/or coronary heart disease.

Based on the above recited facts, then, a method of indicating vasospasm as a forerunner to coronary and hypertensive diseases has been evolved using the flicker fusion threshold of a patient before and after the introduction of approximately 1/150 grains of nitroglycerin or equivaient amounts of a like vasodilating drug to the patient. If an increase in the flicker fusion threshold of a patient occurs after the nitroglycerin therapy, vasospasm is indicated. Normally the optimum detectable difference observable by a patient will occur around four minutes after administration of the nitroglycerin. For assurance, readings may be taken at two minute intervals for approximately-eight minutes, thus insuring an accurate reading. Clinical results have proven this method to be extremely accurate and valuable in diagnosing potential heart disease; in fact I have discovered vasospasm as measured by my invention to be present in over of persons tested having a known or established hypertensive and/or coronary heart disease.

Thus it is seen that a simple and effective means of discovering the presence of vasospasni is provided under this method. This, when coupled with the new and improved testing device described heretofore will make it possible for a doctor to detect vasospasm in a normal routine cnice examination, with little effort and no specialized skill.

Use and operation In detecting vasospasm by means of this device and determining the importance of the findings so far as heart disease is concerned, the following procedure may be followed:

il. patient is given a flicker fusion test by placing him looking at the flickering light rays emitted from the testing machine. A distance of from three to four feet between the patient and the machine has been found to be the most satisfactory. The doctor or operator first turns the proper control knob 23 to a frequency of interrupted iight flashes which is so rapid that it appears to the patient to be a steady beam. The patient is then instructed to tell the operator when the light iirst appears to flicker, the operator meanwhile gradually decreasing the flickering frequency of the light beam by turning the control knob 23 in an opposite direction.

It has been discovered that starting with a steady light and reducing the frequency until the light appears to the patient to icker is operatively more successful than the reverse procedure because of the absence of after image which occurs if the F. F. T. is established by going from the flickering to the steady light.

The frequency at which the patient detects a flickering light is readable directly from the scale of the machine in cycles per second, cycles per minute, or other suitable units. The procedure of reducing the frequency is done several times to enable the patient to become familiar with the change in the appearance of the light and to secure an accurate reading. When three identical and consecutive .readings are obtained, this is taken as the flicker fusion threshold for that patient and may be recorded for later reference by turning the index control knob 28 to move the index pointer 2l to the appropriate position for recording the reading on the index scale 26.

The patient is next given a suitable vasodilatmeans, and a second pointer means adjustable relative to said scale means independently of said control means and arranged for position matching the scale index of said rst pointer means thereby to keep a visible record of said rst pointers scale indication when the rst pointer means is moved to a subsequent position by readjustment of said control means.

References Cited in the le of this patent UNITED STATES PATENTS Number Name Date 1,526,781 Ferree et al Feb. 17, 1925 1,738,708 Howard Dec. 10, 1929 Number Number Name Date Dixey Sept. 20, 1932 Marrison Oct. 11, 1932 Fitzgerald Dec. 13, 1932 Bouln Oct. 17, 1933 Downey Apr. 6, 1943 Renshaw Oct. 29, 1946 Jones July 20, 1948 Draeger et al Jan. 31, 1951 FOREIGN PATENTS Country Date Germany May 16, 1933 

